[go: up one dir, main page]

EP1466144A1 - Elements d'interface et supports pour dispositifs de reseau microfluidique - Google Patents

Elements d'interface et supports pour dispositifs de reseau microfluidique

Info

Publication number
EP1466144A1
EP1466144A1 EP02805626A EP02805626A EP1466144A1 EP 1466144 A1 EP1466144 A1 EP 1466144A1 EP 02805626 A EP02805626 A EP 02805626A EP 02805626 A EP02805626 A EP 02805626A EP 1466144 A1 EP1466144 A1 EP 1466144A1
Authority
EP
European Patent Office
Prior art keywords
nozzle
microfluidic device
channel
microfluidic
sample
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP02805626A
Other languages
German (de)
English (en)
Other versions
EP1466144A4 (fr
Inventor
Sau Lan Tang Staats
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US10/061,001 external-priority patent/US20020100714A1/en
Priority claimed from US10/174,343 external-priority patent/US6800849B2/en
Priority claimed from US10/305,045 external-priority patent/US6864480B2/en
Application filed by Individual filed Critical Individual
Publication of EP1466144A1 publication Critical patent/EP1466144A1/fr
Publication of EP1466144A4 publication Critical patent/EP1466144A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • B01L9/527—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for microfluidic devices, e.g. used for lab-on-a-chip
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44704—Details; Accessories
    • G01N27/44717—Arrangements for investigating the separated zones, e.g. localising zones
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44756—Apparatus specially adapted therefor
    • G01N27/44791—Microapparatus
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation
    • H01J49/167—Capillaries and nozzles specially adapted therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/0036—Nozzles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/021—Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0819—Microarrays; Biochips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/02—Drop detachment mechanisms of single droplets from nozzles or pins
    • B01L2400/027—Drop detachment mechanisms of single droplets from nozzles or pins electrostatic forces between substrate and tip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1039—Micropipettes, e.g. microcapillary tubes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6004—Construction of the column end pieces
    • G01N30/6026—Fluid seals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1074—Multiple transfer devices arranged in a two-dimensional array

Definitions

  • the present invention relates to microfluidic devices, and more
  • microfluidic array devices that can be used to deliver one or more
  • microfluidic device as the microfluidic device is used in a given application are also
  • microfluidic array devices disclosed as well as exemplary uses for the microfluidic array devices.
  • the microfluidic array device is suitable for operations designed for lab-on- a-chip functions including analysis of components in the sample fluid by means of
  • optical spectrometry optical spectrometry, mass spectrometry, etc.
  • microfluidics is considered an
  • microfluidic device which is also often
  • lab-on-a-chip device is a planar device having one or more micron
  • microfluidic features are designed to carry out complex
  • microfluidic devices are to provide microfluidic channels that represent
  • Microfluidic devices have traditionally been fabricated from
  • microfluidic channels that are formed lie parallel to the surface of one
  • planar surface of the substrate, and the channel is sealed by bonding a second planar
  • detecting materials such as analytes, that are disposed in the microfluidic channels
  • microfluidic devices traditionally entails using electroosmotic, electrokinetic and/or
  • microfluidic structure having layered microfluidic channels is possible in terms of its
  • Mass spectrometry provides more chemical information about
  • the material being tested e.g., analytes
  • other single detection techniques e.g., analytes
  • MS mass spectrometry
  • MS-MS a molecule is ionized and analyzed for molecular weight in the first stage of the mass spectrometer, and then the same molecular ion, called the
  • electropipette extends from the edge of the substantially planar substrate.
  • microfluidic channel in this extended region is formed by two planar substrates as in
  • microfluidic channels that are formed in the rest of the microfluidic device.
  • outside dimensions of the tip structure include a thickness that is equal to the
  • microfabrication techniques such as deep ion reactive etching
  • microfluidic devices there are a number of limitations that have equally been
  • microfluidic device having microfluidic features with dimensions less than
  • microfluidic features e.g., channels
  • microfluidic features that have dimensions less than 100 ⁇ m
  • microfluidic array devices incorporating nozzles, that overcome the
  • the present application generally relates to microfluidic devices.
  • a microfluidic device includes a body having a first surface and an opposing second surface. At least one channel is
  • the microfluidic device further includes at least one nozzle that
  • the nozzle is disposed along the second surface.
  • the nozzle is in fluid communication with one
  • each channel terminates in a nozzle opening that is formed as part
  • the exemplary embodiment Unlike traditional microfluidic devices, the exemplary
  • microfluidic device has one or more channels that are open at each end and are
  • the nozzle is conically shaped with the
  • the nozzle opening has a diameter equal to or less than 100
  • ⁇ m preferably equal to or less than 50 ⁇ m and more preferably, equal to or less
  • the microfluidic nozzle array device is formed by an injection molding process that permits the microfluidic nozzle array device to have the above
  • microfluidic device and providing an interface between the at least one microfluidic
  • the at least one microfluidic device has a
  • the member includes a body having an upper face and a lower face and a plurality of open well members formed therein.
  • Each well member is defined by a well wall and includes a first end and an opposing
  • the apparatus includes a microfluidic
  • the device having a body including a first surface and an opposing second surface.
  • body has at least one channel formed therein and extending through the body from
  • the nozzle is in fluid communication with the channel such that one end of
  • the channel terminates in a nozzle opening that is formed as part of a tip of the
  • the apparatus also includes a frame disposed around a periphery of the microfluidic device such that the microfluidic device is securely held therein and a
  • first and second retaining members spaced apart a sufficient distance
  • the frame to be disposed between and held in place by the first and second retaining members, wherein in a retained position, the at least one nozzle is
  • a shield is coupled to at least one of the
  • the shield has at least one aperture formed therein which is in
  • the shield is utilized as a
  • Fig. 1 is a top perspective view of a microfluidic device having an
  • FIG. 2 is a cross-sectional view taken along the line 2-2 of Fig. 1;
  • Fig. 3 is a top plan view of the microfluidic device according to Fig. 1 illustrating placement of electrodes around the nozzles and the connections
  • Fig. 4 is a top perspective view of a microfluidic device having an
  • Fig. 5 is a cross-sectional view of the microfluidic device according
  • Fig. 6 is a perspective view of an exemplary mold used to
  • Fig. 7 is a cross-sectional view of first and second dies in a closed
  • Fig. 8 is a cross-sectional view of first and second dies of the mold
  • Fig. 9 is a cross-sectional view illustrating a mold arrangement for
  • Fig. 10 is a top plan view of a tile arrangement formed of a number
  • each strip including a nozzle array
  • one of the strips is removed and placed in close proximity to a mass spectrometer
  • Fig. 11 is a cross-sectional view of one microfluidic channel/nozzle
  • a sample reservoir is sealed by a member having a polymeric cover sheet which is msertable and movable within the reservoir for discharging the
  • Fig. 12 is a cross-sectional view of one microfluidic channel/nozzle
  • sealing base which is insertable and movable within the reservoir for discharging the
  • Fig. 13 is a cross-sectional view of one microfluidic channel/nozzle
  • Fig. 14 is a top plan view of an exemplary microfluidic nozzle array
  • Fig. 15 is a cross-sectional view taken along the line 14-14;
  • Fig. 16 is a cross-sectional side elevational view illustrating the
  • microfluidic device of Fig. 5 being used in UV spectrophotometry
  • Fig. 17 is a top plan view of a retaining base for releasably holding a
  • Fig. 18 is a cross-sectional view taken along the line 18-18 of Fig.
  • Fig. 19 is a top plan view of a retaining base according to another
  • Fig. 20 is a cross-sectional view of an interface plate that can be used
  • Fig. 21 is a cross-sectional view of a microfluidic device having an array of nozzles
  • Fig. 22 is a cross-sectional view of an interface plate according to
  • Fig. 23 is a top plan view of a mass spectrometer unit and an
  • Fig. 24 is a front elevational view of the microfluidic device of Fig.
  • Fig. 25 is a side elevational view of the microfluidic device of Fig.
  • Fig. 26 is a top view of a holder for securely retaining the
  • microfluidic device of Fig. 24
  • Fig. 27 is a side elevational view of the holder of Fig. 26;
  • Fig. 28 is a top view of the holder of Fig. 26 with the microfluidic
  • Fig. 29 is a side elevational view of a nanospray device interface in a
  • Fig. 30 is a perspective view of a holder for securely holding a
  • microfluidic device and being coupled to an apparatus that has a degree of
  • Fig. 31 is a front elevational view of a microfluidic device having an
  • Fig. 32 is a sectional view through one nozzle and its associated
  • Fig. 33 is a cross-sectional view through a microfluidic device to
  • Fig. 34 is a front elevational view of a microfluidic device with frame according to another exemplary embodiment
  • Fig. 35 is a side elevational view of the microfluidic device.
  • Fig. 36 is a front elevational view of a microfluidic device with frame
  • the microfluidic device 10 has a
  • substrate body 20 that is formed of a polymeric material, as will be described in
  • microfluidic channel 30 that is formed
  • the substrate body 20 has a first surface
  • channel 30 extends the complete thickness of the substrate body 20.
  • microfluidic channel 30 is thus open at both a first end 32 at the first surface 22 and a second end 34 at the second surface 24.
  • channel 30 is formed in a protrusion 50 that is formed on the second surface 24 of
  • the protrusion 50 is a protrusion of the substrate body 20. According to one exemplary embodiment, the protrusion 50
  • the tapered protrusion 50 serves as a nozzle that delivers a sample (i.e.,
  • the microfluidic channel 30 is formed in a perpendicular manner in the
  • microfluidic channel 30 is preferably formed so that it
  • nozzles 50 can be formed in one substrate body 20.
  • the microfluidic channels 30 are formed in one substrate body 20.
  • a plurality of microfluidic channels/nozzles are arranged in
  • microfluidic channels/nozzles are arranged in an 8x12 grid with spacing of about 9
  • microfluidic channels/nozzles are placed in a 16x24 grid with spacing of
  • FIG. 2 generally illustrates a section of a
  • each nozzle 50 is
  • the first end 32 of the microfluidic channel 30 is in the form
  • a reservoir 60 i.e. , an annular cavity
  • the intermediate channel section 36 also has a tapered
  • microfluidic channel 30 are greatest at the first end 32, where the reservoir is
  • microfluidic channel 30 formed in nozzle 50 has an inside diameter of about 100 ⁇ m
  • microfluidic channel 30 opens gradually in a direction away from the nozzle 50 to
  • length of the microfluidic channel 30 can be tailored to a given application
  • first end 32 defined at first end 32 and also the thickness of the substrate body 20.
  • the microfluidic channel 30 has a length of about 3 mm or greater.
  • the aforementioned dimensions are merely recited to illustrate
  • microfluidic device 10 one exemplary embodiment and it will be understood that the microfluidic device 10
  • the volume of the reservoir 60 should be such that it can hold an
  • microfluidic devices are designed for. For example, the sample volume that is used
  • sample material is from sub-microliter up to 10 microliters for mass spectrometer analysis using electrospray. As will be described in greater detail hereinafter, the sample material
  • the outside diameter of the protruding nozzle 50 also accordingly
  • channel 30 by injecting or otherwise disposing the sample into one or more
  • reservoirs 50 and then transporting the sample through the associated microfluidic channel 30 using techniques described in greater detail hereinafter.
  • the microfluidic device 10 can be fabricated
  • Electrospray is achieved by subjecting the nozzle 50 to
  • sample liquid and analytes
  • the microfluidic device 10 includes a conductive
  • conductive region can extend onto the second surface 24.
  • the area around each nozzle 50 up to the extreme end of the nozzle 50 is metallized by
  • the conductive region 70 takes the form of a ring-
  • the conductive region 70 can vary depending upon the precise application; however,
  • the conductive region 70 should have a sufficient thickness so that when an electric
  • the sample material i.e., a liquid
  • microfluidic channel vaporizes and therefore can be used in electrospray
  • nanospray applications such as electrospray ionization of analytes for a mass
  • the microfluidic device 10 in this example, provides a low cost
  • disposable electrospray interface capable of nanospray. This device can be fabricated to accommodate more than one sample input in order to multiplex several
  • Each of the conductive regions 70 formed around the nozzles 50 is
  • the electrical contacts 80 are preferably in the form of
  • Fig. 3 shows one exemplary method of electrically
  • one conductive region 70 is electrically connected via an
  • the contact 80 and is therefore formed of a conductive material (e.g., a metal).
  • the electrical pathway 90 can be in the form of a thin conductive film.
  • the voltage used to form the spray is about 5-6 KN
  • a tip portion 52 having an outside diameter from about 50 ⁇ m to 80 ⁇ m. It will be appreciated that larger sized outside diameters can be used; however, this will require a greater voltage to be applied to the nozzle 50 in order to form a spray.
  • the microfluidic device 100 is
  • microfluidic device 100 includes a substrate body 110 that is formed of a polymeric
  • the first and second faces 120, 130 are not
  • the microfluidic device 100 has at least one microfluidic channel 140
  • the first face 120 includes a first perimeter wall 122 that
  • the microfluidic device 100 is generally square shaped; however, this is merely one exemplary shape for the microfluidic
  • microfluidic device 100 as the microfluidic device 100 can assume any number of different
  • one or more reservoirs are defined within the boundary of the first perimeter wall 122.
  • walls 124 are formed with the number of reservoir walls 124 equal to the number of
  • microfluidic channels 140 formed in the substrate body 110.
  • 124 partially defines a reservoir 160 that is designed to hold a sample material
  • the reservoir wall 124 therefore also defines the first end 142 of the microfluidic
  • first end 142 of the microfluidic device 140 is therefore formed above the planar
  • the second end 144 of the microfluidic channel 140 is formed in a
  • protrusion 170 that extends outwardly from the second face 130.
  • the protrusion 170 preferably has a tapered shape (inward taper) such
  • the nozzle 170 acts as a nozzle that can discharge a sample that is loaded into the microfluidic channel 140 (e.g. , in the reservoir 160).
  • the nozzle 170 is therefore part of the
  • microfluidic channel structure since the microfluidic channel 140 is formed
  • the second face 130 is also not substantially planar but rather
  • a second perimeter wall 132 that extends at least partially around a
  • the second face 130 does contain a floor 134 that
  • base sections 180 are formed with the number of nozzle base sections 180 being
  • the nozzle base sections 180 are
  • each nozzle base section 180 has a generally annular shape.
  • the shape of the nozzle base section 180 is not limited to an annular shape and instead can have any number of shapes, including a conical shape or a tapered
  • a first shape or any other regular or irregular shape. According to one embodiment, a
  • nozzle 170 therefore extends beyond the upper edge of the second perimeter wall
  • the diameter of the reservoir 160 is about equal to the outside diameter of the nozzle base section 180; and therefore, an
  • outside diameter of the reservoir wall 124 is greater than the outside diameter of the
  • microfluidic channel 140 is in the form of the reservoir 160.
  • a distal end of the reservoir 160 has an inwardly tapered construction that leads to an intermediate
  • the intermediate channel section 146 also serves as a substantial length of the intermediate channel section 146. A substantial length of the intermediate channel section 146 is formed in the nozzle base section 180. The intermediate channel section 146 also serves as a substantial length of the intermediate channel section 146.
  • microfluidic channel 140 are greatest at the first end 142 and are at a minimum at a
  • nozzle 170 is generally cylindrical in shape along its length. According to one
  • the formed at the tip portion 172 has an inside diameter equal to or less than 100 ⁇ m
  • microfluidic channel 140 varies along its length due to its tapered construction. For example, the inside diameter of the microfluidic channel 140 opens gradually in a
  • channel 140 traverses through the thickness of the substrate body 110 and
  • the microfluidic channel 140 is formed to a diameter of about 1.5 mm to
  • the length of the microfluidic channel 140 can be tailored
  • the length of the microfluidic channel 140 is about 3 mm; however, this will vary depending upon the thickness of
  • the device 100 the amount of sample that is to be loaded into the device, etc.
  • the microfluidic channel 140 is formed
  • microfluidic channel 140 is formed substantially perpendicular to both the first and
  • the nozzle 170 extends beyond a plane containing the distal edge of the second perimeter wall 132, the distal end of the reservoir wall
  • 124 preferably lies within the same plane that contains the distal edge of the first perimeter wall 122. This orientation permits a cover (e.g., thin polymeric cover
  • microfluidic channel is closed by the bonding of one layer over another layer.
  • the present device 100 is injection-molded, separate bonded layers are not required.
  • Figs. 1-5 are merely exemplary in nature and are
  • the nozzle structures do not necessarily have to have conical shapes; however, for ease of
  • microscale nozzle dimensions e.g., a nozzle tip opening
  • nozzle as measured at a tip portion thereof, is less than about 150 ⁇ m and
  • preferably is equal to or less than about 100 ⁇ m, and more preferably equal to or
  • microfluidic array devices are particularly useful as the present microfluidic array devices.
  • microfluidic array is suited to inexpensive fabrication methods. More specifically, the microfluidic array
  • devices of the present application can be manufactured by injection molding a
  • thermoplastic using conventional injection molding techniques.
  • thermoplastics include poly cyclic olefin polyethylene copolymers, poly methyl
  • PMMA methacrylate
  • polymers such as Surlyn ® and Bynel ® .
  • Poly cyclic olefin polyethylene co-polymers are particularly suitable for use in an injection
  • Topas ® which is a polyethylene-polycyclic olefin co-
  • PBT polybutyl terephthalate
  • polyamides such as nylons of different grades (nylon 6-6, nylon, 6 nylon 6-12,
  • thermoplastic polymers with a
  • these polymers preferably also have a high melt viscosity
  • thermoplastics blended with a lubricant e.g. , liquid crystalline polymers
  • crystalline polymers containing polymers such as Zenite ® (DuPont Company) and
  • elastomers may also be suitable.
  • mold structure is readily changeable and is dictated by the desired construction of the microfluidic device and more particularly, the desired
  • microfluidic channels based on the shape, dimensions and other
  • the mold typically is formed of several parts that mate with one
  • the mold or mold insert is typically formed as a negative impression of whatever channel architecture or device features are
  • a polymeric material is injected into the microfluidic array device.
  • the mold is formed of two mold
  • the mold i.e., mold dies
  • mold insert can be prepared from any material
  • the channel architecture can be achieved by techniques, such as photolithographic
  • the mold or mold insert is formed as a negative impression of the channel architecture by electroforming metal and the metal mold is polished
  • the mold for injection molding, the mold can be made of
  • microfluidic design features can be formed in the mold through photolithography
  • some ceramics can be used to fabricate the mold or mold insert.
  • Molds can also be fabricated from a "rapid prototyping" technique
  • resulting polymer-based mold can be electroformed to obtain a metallic negative
  • nickel commonly used metal for electroforming is nickel, although other metals can also be used.
  • the metallic electroformed mold is preferably polished to a high degree of
  • abrasives e.g. , diamond particles. Electropolishing and other forms of
  • polishing can also be used to obtain the same degree of finish. Additionally, the
  • metallic mold surface should preferably be as planar and as parallel as the Si, glass,
  • the metallic mold is
  • FIG. 6 is a perspective view of a mold construction 200 that is constructed to injection mold a microfluidic nozzle array
  • the mold 200 is formed as a negative impression of the microfluidic
  • the mold 200 includes a first mold die or part 210 and
  • a second mold die or part 230 that are constructed so that they are complementary to
  • microfluidic nozzle array device similar to device 10 illustrated in
  • the mold 200 is preferably formed by electric discharge machining (EDM).
  • EDM electric discharge machining
  • the first mold die 210 has a first face 212 that includes a
  • the first face 212 has a recessed section 214 formed
  • the recessed section 214 generally defines the outer peripheral shape of the
  • microfluidic device and also the depth of the recessed section 214 defines the
  • the microfluidic device typically has a square or rectangular shape
  • the shape of the recessed section 214 will be the same or similar.
  • the illustrated recessed section 214 is generally square shaped.
  • each pin 216 directly corresponds to
  • a base section 217 is closed and the polymeric material is injected. More specifically, a base section 217
  • intermediate section 218 corresponds to the intermediate section of the microfluidic
  • the dimensions of the pin 216 are greatest at the base section 217 and the pin
  • the pins 216 are preferably spaced in arrays.
  • the second mold die 230 has a first face
  • the first face 232 is
  • the apertures 234 are arranged according to a
  • apertures 234 are sized so that they receive at least a portion of the conical tip
  • first and second mold dies 210, 230 mate with one another.
  • the apertures 234 are themselves contoured so that the apertures 234 taper inwardly with a lower portion
  • each aperture 234 having a conical shape so as to form the conical nozzle of
  • tip sections 219 of the pins 216 extend completely to the bottom of the apertures 234
  • the mold 200 of Fig. 6 is constructed to generally produce the
  • microfluidic device 10 of Fig. 1
  • Fig. 7 shows a cross-sectional view of a mold that is constructed to
  • first and second mold dies 210, 230 dictate the dimensions and shape of the first and second mold dies 210, 230
  • dies 210, 230 are closed and any preparation steps that are necessary for the
  • second mold die 220 seat against one another to effectively seal the recessed section
  • the polymeric material typically a resin
  • Fig. 7 shows a cross-
  • first and second mold dies 210, 230 are negative impressions of the first and second mold dies 210, 230
  • the microfluidic channel will take the form of the pin
  • the nozzle is formed by resin filling completely
  • the conically lower shaped portion 235 are in contact with one another.
  • Mold 200 is intended to be used a number of times over a period of
  • a material should be selected that permits microsc'ale features to be formed in the microfluidic device and also permits a great number of microfluidic
  • fabricating the mold 200 is hardened steel. With conventional machining
  • EDM electric discharge machining
  • tip section 219 can be limited due to manufacturing considerations. The available
  • this space is
  • first mold die 210 is illustrated as having a square shape
  • first mold die 210 can be formed to have any number
  • mold die 230 permit these two components to mate with one another.
  • the pressure of the injected resin is adjusted such that the resin does not fill the entire space in the gap
  • the tip section 219 can have a diameter greater than
  • Fig. 9 illustrates one exemplary method of overshooting the injected
  • the nozzle opening 215 is defined by pressure used to
  • the dimensions of the nozzle opening can be controlled.
  • microfluidic nozzle array device is arranged to have the
  • plates consist of regularly spaced sample input points in a grid pattern.
  • microfluidic nozzle array devices can be formed and then combined
  • sample reservoirs also referred to as sample wells or sample inputs
  • some common microfluidic devices contain 96
  • sample reservoirs (8x12 grid); 384 sample reservoirs (16x24 grid); and 1536 sample
  • the subunit structures can be formed as
  • strip can be formed to include 2 rows of spaced apart nozzles.
  • the user can be supplied with a base plate that has a
  • the base plate can contain pre ⁇
  • nozzle subunit structures are securely held within the base plate and are arranged
  • structures can contain interlocking features to provide an interlocking connection
  • base plate functions as a base on which the final microfluidic nozzle array device can be constructed by arranging a number of nozzle subunit structures together and
  • Fig. 17 structure for releasably holding the nozzle subunits in an interlocked manner is illustrated in Fig. 17 and is discussed in greater detail hereinafter in the discussion
  • one nozzle subunit structure contains 4 reservoirs and therefore, if the
  • nozzle spray configuration is to have the nozzle spray "off-axis", i.e., the nozzle sprays in a direction perpendicular to the inlet. Since the nozzle has to be placed in close
  • a tiled microfluidic nozzle array microtiter plate can be used for electrospray in the off-axis configuration.
  • the nozzle mount holds the strip 302 and has at least an x-y translation stage
  • each of the nozzles can be placed in an optimal position with respect to the
  • the nozzles 310 are positioned below the center line of the mass
  • microfluidic nozzle array devices disclosed herein are suitable
  • the microfluidic nozzle array device 100 is particularly suited for use
  • Electrospray is the technique that enables a liquid sample to be vaporized and ionized for mass spectrometry analysis.
  • a high voltage e.g., 4-5 KV
  • capillary is driven generally by a pump, such as a syringe pump.
  • the opening is filled with a sample to be sprayed. Before the spray, the reservoir has to
  • reservoir 160 i.e., the open first end 142 of the microfluidic channel 140
  • the sealing of the open end of the reservoir 160 can be accomplished in a
  • FIGs. 11-13 illustrate a number of exemplary ways to provide the desired liquid tight seal
  • FIG. 11 illustrates a first sealing technique in which the
  • the elastic cover sheet 400 is preferably
  • the polymeric cover sheet 400 is coupled to the reservoir wall 124 so
  • a mechanical plunger 410 or the like can be used to apply a force to
  • the polymeric cover sheet 400 to force the sample along the length of the
  • microfluidic channel 140 and ultimately out of the nozzle opening (second end 144
  • cover sheet 400 and the plunger 410 is illustrate by arrow 420.
  • a movable sealing member 400 is provided and is formed of a sealing base 422 for sealing the opening of the reservoir and a rod or plunger 444 that is
  • sealing base 442 attached to the sealing base 442.
  • the dimensions of the sealing base 442 are greater
  • base 442 seats against the reservoir wall 124 and completely extends across the open
  • the sealing base 442 is formed of a suitable elastic
  • sealing base 442 to act as a temporary diaphragm that seals the reservoir as the sealing base 442 is directed into the reservoir 160 itself.
  • the sealing base 442 deforms as it is forced into the first end
  • the sealing base 442 includes a flange 446 that has a
  • vent can be fabricated using conventional vent technology in that the vent should permit
  • plunger 444 can either be manually
  • the member 450 has a hollow
  • the member 450 includes a distal end 452 which initially is positioned
  • a gasket 460 is positioned proximate to the open end of the reservoir 160.
  • a gasket 460 is positioned at the distal end 452.
  • the gasket 460 is in the form of a
  • the gasket 460 serves to provide a seal between the
  • the gasket 460 is disposed around the bore
  • the sample is moved within the microfluidic
  • a high-pressure gas such as air or dry nitrogen gas that is delivered
  • a protective cover (not shown) can be
  • the protective cover must be
  • the sample transport the sample along the microfluidic channel 140.
  • the microfluidic channel 140 transport the sample along the microfluidic channel 140.
  • protective cover can be in the formed of a thin polymeric film that is gas permeable
  • a more conventional fluid delivery mechanism can be used with the
  • a stopper is inserted into the reservoir 160, with
  • the stopper having a bore formed therethrough which is in communication with the
  • a capillary is inserted through the bore and the liquid sample is
  • the sample is not stored in the reservoir 160 but rather is delivered to the channel 140 by being injected into the reservoir 160
  • the front face of the nozzle array is made
  • Liquids that are suitable for use in electrospray mass spectrometry analysis include but are
  • nitrogen gas to the nozzle opening may be easily added in a polymer substrate
  • FIGs. 14-15 are a top plan view and a
  • the microfluidic nozzle array device 500 can be similar to or
  • a gas outlet 522 is formed such that it is concentric with one nozzle 530.
  • substrate 510 with the nebulizing gas channels can be fabricated by an injection
  • the substrate 510 can be any suitable material that can be fabricated first and then later attached to (e.g. , bonded) the nozzle array device 500 as a separate component.
  • the substrate 510 can be any suitable material that can be fabricated first and then later attached to (e.g. , bonded) the nozzle array device 500 as a separate component.
  • the substrate 510 can be any suitable material that can be fabricated first and then later attached to (e.g. , bonded) the nozzle array device 500 as a separate component.
  • the substrate 510 can be any suitable substrate 510 fabricated first and then later attached to (e.g. , bonded) the nozzle array device 500 as a separate component.
  • the substrate 510 can be any suitable material that can be fabricated first and then later attached to (e.g. , bonded) the nozzle array device 500 as a separate component.
  • the substrate 510 can be any suitable material that can be fabricated first and then later attached to (e.g. , bonded) the nozzle array device
  • the sample can be fed to the nozzle by the elutant of a high performance liquid phase gas
  • the reservoir size in the nozzle array can be formed to arbitrary sizes, it can be formed so that the open end of the reservoir
  • the reservoir side of the nozzle array can
  • the driving force for the liquid sample analytes to flow through the nozzle
  • opening in this case is the pressure-driven liquid flow of the HPLC.
  • microfluidic nozzle array devices disclosed herein are also particularly adapted to be used as a nozzle array for optical spectrometry. Since
  • each microfluidic channel in the nozzle array device terminates with a nozzle
  • array device is formed of a polymeric material which is generally hydrophobic
  • microfluidic channel contains within the liquid in the microfluidic channel.
  • optical material in its design. This results in reduced structural complexity for the microfluidic nozzle array device and also a reduction in both cost and complexity
  • a 96 microtiter nozzle plate filled with samples can be placed in an
  • UV spectrophotometry must have a sample well bottom made of a special UV
  • Fig. 16 is a cross-sectional view illustrating how the microfluidic
  • nozzle array device 100 can be used for UV spectrophotometry.
  • Fig. 16 illustrates
  • microfluidic nozzle array device 100 in partial section showing two nozzle
  • UV light is emitted from a source 540 and travels toward the microfluidic nozzle array device 100 and
  • the UV light travels through the sample (e.g., liquid and analytes).
  • sample e.g., liquid and analytes
  • the device 100 can easily be disposed between a UV light source and the detector 550 of
  • the present microfluidic nozzle array device does not have to be formed of an
  • optically transparent material This reduces the complexity of the fabrication process since this requirement is not present in the microfluidic nozzle array device.
  • microfluidic nozzle array devices disclosed herein also
  • microfluidic nozzle array device has typically been used.
  • the microfluidic nozzle array device has typically been used.
  • the metallic capillary has a tendency to "spring"
  • Spotting is typically carried out with a row of eight to twelve capillaries using an expensive machine and the capillaries are rinsed and reused for different DNA samples.
  • microfluidic nozzle array devices disclosed herein have
  • microfluidic nozzle array devices in comparison to the conventional metal
  • the injection-molded microfluidic nozzle array devices can be any suitable material.
  • the injection-molded microfluidic nozzle array devices can be any suitable material.
  • DNA or protein molecules are not adsorbed on the walls of the
  • a two dimensional nozzle spotter can be
  • polymeric nozzle can be assisted by pumping the molecules out of the nozzle with
  • microfluidic nozzle array device can also be used for spotting the
  • MALDI matrix-assisted laser desorption ionization
  • fragments of high molecular weight, the molecules to be analyzed are deposited on a
  • UV-absorbant molecules that can be vaporized by a UV laser.
  • the molecules of interest are thus carried into the gas phase and are
  • the matrix material is
  • the spraying allows the matrix molecules and the molecules of interest to be
  • the spotting of the MALDI plate may also be
  • the density of the nozzle array can be greatly increased and this permits the density of
  • the spotting array to be increased. Accordingly, more testing or experimental sites
  • the electric field can be generated by using the arrangement illustrated in
  • a mold can be fabricated and
  • resin can be injected into the mold to form pipette tips that have an elongated body
  • tip section that has a tip opening having an inside diameter of less than about 20 ⁇ m (with the tip section having an outside diameter of less than about
  • a polymeric microfluidic nozzle array device is fabricated using the
  • the mold is formed of a metal and a conical surface of the mold that
  • the conical surface is
  • microfluidic device that is formed as part of the microfluidic device.
  • the microfluidic device is
  • PBT polybutyl terephthalate
  • the microfluidic nozzle array device is formed
  • nozzles that have an average outside diameter of about 60 microns and an
  • average inside diameter of the tip i.e., the diameter of the nozzle opening
  • the diameter of the nozzle opening being less than about 20 microns.
  • the outer surface of the nozzle is made much smoother and further the shape of the
  • nozzles is more consistent from nozzle to nozzle and from mold run to mold run.
  • microfluidic device which have microscale features.
  • microfluidic nozzle array device is then used as an electrospray
  • a voltage of between 5-6 KV is applied to a
  • the vaporized, ionized sample is then injected into an inlet of a mass
  • a polymeric microfluidic nozzle array device is fabricated using the
  • the mold is formed of a metal and a conical surface of the mold that
  • the conical surface is
  • microfluidic device that is formed as part of the microfluidic device.
  • the microfluidic device is
  • PBT polybutyl terephthalate
  • microfluidic nozzle array device is formed
  • nozzles that have an average outside diameter of about 60 microns and an
  • the mold is constructed so that a microfluidic nozzle
  • array strip is formed having two rows of twelve nozzles each.
  • microfluidic nozzle array strips are then placed side by side and adjacent strips are
  • an adhesive e.g. , glue
  • the edges are heated so that the polymeric
  • the fused bond between adjacent strips includes a weakened section
  • a score line or the like can be formed along the bond or the thickness of the
  • bonded interface section between the two strips can be of reduced thickness
  • one strip can easily be detached from the other strip. Any remaining microfluidic
  • microfluidic devices The number of bonded microfluidic nozzle array strips will be used. The number of bonded microfluidic nozzle array strips will be used.
  • microfluidic nozzle array device vary depending upon the desired overall size of the microfluidic nozzle array device
  • microfluidic device In use, the single, tiled microfluidic nozzle array device is
  • a polymeric microfluidic nozzle array device is fabricated using the
  • the mold is formed of a metal and a conical surface of the mold that
  • the conical surface is
  • microfluidic device that is formed as part of the microfluidic device.
  • the microfluidic device is
  • PBT polybutyl terephthalate
  • the microfluidic nozzle array device is formed
  • nozzles that have an average outside diameter of about 60 microns and an
  • the mold is constructed so that a microfluidic nozzle array strip is formed having two rows of twelve nozzles each.
  • 17 generally illustrates the concept of tiling or otherwise combining a number of
  • a base plate 600 is provided and serves as the means for receiving a
  • the base plate 600 is a frame-like member having a predetermined number of retaining rails 620 that are affixed at their ends to a pair of
  • the rails 620 are spaced apart from one another so that open slots 640 are formed between adjacent rails 620.
  • each rail 620 has a number of clamping features 650 formed as a part thereof and spaced along the length of the
  • the clamping feature 650 includes side walls 652 that are spaced apart
  • the entire length of the rail 620 can have a "U-shaped"
  • the entire rail 620 serves as locking member instead of discrete clamping features 650 that are spaced along its
  • nozzles 612 are illustrated as
  • the structure 610 can be releasably
  • the nozzle subunit structures 610 are releasably interlocked with the

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Electrochemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Dispersion Chemistry (AREA)
  • Plasma & Fusion (AREA)
  • Engineering & Computer Science (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
  • Optical Measuring Cells (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

La présente invention concerne un élément conçu pour soutenir au moins un dispositif microfluidique et pour offrir une interface entre ce dispositif microfluidique et un second dispositif. Une pluralité de réservoirs se trouve dans ledit dispositif microfluidique et ledit élément comprend un corps qui présente une face supérieure et une face inférieure et à l'intérieur duquel est ménagée une pluralité d'éléments de puits ouverts. Chaque élément de puits est défini par une paroi de puits et présente une première extrémité et une seconde extrémité opposée, qui est conçue et dimensionnée pour venir en prise par frottement avec ledit dispositif microfluidique, de façon qu'au moins certains des éléments de puits ouverts et des réservoirs du dispositif microfluidique s'alignent les uns sur les autres. La présente invention concerne également un appareil pour assurer l'interface avec un spectromètre de masse, afin d'effectuer une application par nanopulvérisation.
EP02805626A 2001-12-19 2002-12-18 Elements d'interface et supports pour dispositifs de reseau microfluidique Withdrawn EP1466144A4 (fr)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US61001 1998-04-14
US34106901P 2001-12-19 2001-12-19
US341069P 2001-12-19
US10/061,001 US20020100714A1 (en) 2001-01-31 2002-01-30 Microfluidic devices
US10/174,343 US6800849B2 (en) 2001-12-19 2002-06-17 Microfluidic array devices and methods of manufacture and uses thereof
US174343 2002-06-17
US305045 2002-11-26
US10/305,045 US6864480B2 (en) 2001-12-19 2002-11-26 Interface members and holders for microfluidic array devices
PCT/US2002/040575 WO2003054488A1 (fr) 2001-12-19 2002-12-18 Elements d'interface et supports pour dispositifs de reseau microfluidique

Publications (2)

Publication Number Publication Date
EP1466144A1 true EP1466144A1 (fr) 2004-10-13
EP1466144A4 EP1466144A4 (fr) 2007-09-05

Family

ID=27490169

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02805626A Withdrawn EP1466144A4 (fr) 2001-12-19 2002-12-18 Elements d'interface et supports pour dispositifs de reseau microfluidique

Country Status (5)

Country Link
EP (1) EP1466144A4 (fr)
JP (1) JP4439916B2 (fr)
AU (1) AU2002366697A1 (fr)
CA (1) CA2470847A1 (fr)
WO (1) WO2003054488A1 (fr)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6803568B2 (en) 2001-09-19 2004-10-12 Predicant Biosciences, Inc. Multi-channel microfluidic chip for electrospray ionization
US7105810B2 (en) 2001-12-21 2006-09-12 Cornell Research Foundation, Inc. Electrospray emitter for microfluidic channel
CA2521999A1 (fr) 2002-12-20 2004-09-02 Biotrove, Inc. Appareil et procede de dosage utilisant des reseaux microfluidiques
US7007710B2 (en) 2003-04-21 2006-03-07 Predicant Biosciences, Inc. Microfluidic devices and methods
US7537807B2 (en) 2003-09-26 2009-05-26 Cornell University Scanned source oriented nanofiber formation
WO2005059178A1 (fr) * 2003-12-10 2005-06-30 Bio Trove, Inc. Ligature selective amelioree et essai d'amplification
US20060060769A1 (en) 2004-09-21 2006-03-23 Predicant Biosciences, Inc. Electrospray apparatus with an integrated electrode
US7591883B2 (en) 2004-09-27 2009-09-22 Cornell Research Foundation, Inc. Microfiber supported nanofiber membrane
GB0517910D0 (en) * 2005-09-05 2005-10-12 Enigma Diagnostics Ltd Liquid transfer device
JP4984729B2 (ja) * 2006-08-07 2012-07-25 東レ株式会社 帯電防止性カバーを有するマイクロアレイ
WO2010040227A1 (fr) 2008-10-10 2010-04-15 The Governing Council Of The University Of Toronto Dispositifs microfluidiques hybrides numériques et à canal et procédés d'utilisation associés
US10232374B2 (en) 2010-05-05 2019-03-19 Miroculus Inc. Method of processing dried samples using digital microfluidic device
CN108026494A (zh) 2015-06-05 2018-05-11 米罗库鲁斯公司 限制蒸发和表面结垢的空气基质数字微流控装置和方法
US10695762B2 (en) 2015-06-05 2020-06-30 Miroculus Inc. Evaporation management in digital microfluidic devices
US10184102B2 (en) * 2015-08-26 2019-01-22 EMULATE, Inc. Controlling pressure
EP3500660A4 (fr) 2016-08-22 2020-03-04 Miroculus Inc. Système de rétroaction permettant la maîtrise des gouttelettes en parallèle dans un dispositif microfluidique numérique
WO2018126082A1 (fr) 2016-12-28 2018-07-05 Miroculis Inc. Dispositifs microfluidiques numériques et procédés
WO2018187476A1 (fr) 2017-04-04 2018-10-11 Miroculus Inc. Appareils microfluidiques numériques et procédés de manipulation et de traitement de gouttelettes encapsulées
EP3658908B1 (fr) 2017-07-24 2025-11-12 Integra Biosciences AG Systèmes microfluidiques numériques et procédés à dispositif de collecte de plasma intégré
CN111587149B (zh) 2017-09-01 2022-11-11 米罗库鲁斯公司 数字微流控设备及其使用方法
EP3796999A4 (fr) 2018-05-23 2022-03-09 Miroculus Inc. Contrôle de l'évaporation dans la microfluidique numérique
EP3917670A4 (fr) 2019-01-31 2022-11-02 Miroculus Inc. Compositions anti-encrassement et procédés de manipulation et de traitement de gouttelettes encapsulées
EP3953041A4 (fr) 2019-04-08 2023-01-25 Miroculus Inc. Appareils microfluidiques numériques à cartouches multiples et procédés d'utilisation
US11524298B2 (en) 2019-07-25 2022-12-13 Miroculus Inc. Digital microfluidics devices and methods of use thereof
US11772093B2 (en) 2022-01-12 2023-10-03 Miroculus Inc. Methods of mechanical microfluidic manipulation

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9521775D0 (en) * 1995-10-24 1996-01-03 Pa Consulting Services Microwell plates
US6068751A (en) * 1995-12-18 2000-05-30 Neukermans; Armand P. Microfluidic valve and integrated microfluidic system
AU726987B2 (en) * 1996-06-28 2000-11-30 Caliper Life Sciences, Inc. Electropipettor and compensation means for electrophoretic bias
US6136212A (en) * 1996-08-12 2000-10-24 The Regents Of The University Of Michigan Polymer-based micromachining for microfluidic devices
US6137501A (en) * 1997-09-19 2000-10-24 Eastman Kodak Company Addressing circuitry for microfluidic printing apparatus
WO1999015876A1 (fr) * 1997-09-19 1999-04-01 Aclara Biosciences, Inc. Systeme et procede de transfert de liquides
US6165417A (en) * 1998-10-26 2000-12-26 The Regents Of The University Of California Integrated titer plate-injector head for microdrop array preparation, storage and transfer

Also Published As

Publication number Publication date
WO2003054488A1 (fr) 2003-07-03
EP1466144A4 (fr) 2007-09-05
JP4439916B2 (ja) 2010-03-24
JP2005513465A (ja) 2005-05-12
AU2002366697A1 (en) 2003-07-09
CA2470847A1 (fr) 2003-07-03

Similar Documents

Publication Publication Date Title
US6864480B2 (en) Interface members and holders for microfluidic array devices
US6800849B2 (en) Microfluidic array devices and methods of manufacture and uses thereof
JP4439916B2 (ja) マイクロ流体アレイ・デバイス用インターフェース部材およびホルダ
US7618576B2 (en) Microfluidic array devices and methods of manufacture thereof
US7303727B1 (en) Microfluidic sample delivery devices, systems, and methods
US6284113B1 (en) Apparatus and method for transferring liquids
US5872010A (en) Microscale fluid handling system
Wang et al. Microfluidics-to-mass spectrometry: a review of coupling methods and applications
US7034854B2 (en) Methods and apparatus for ink delivery to nanolithographic probe systems
US10486156B2 (en) Fluid transfer from digital microfluidic device
US20020100714A1 (en) Microfluidic devices
WO1997004297A9 (fr) Systeme permettant des transferts de micro-quantites de fluide
US20030026740A1 (en) Microfluidic devices
US20030049177A1 (en) Method and apparatus for electrostatic dispensing of microdroplets
WO2002063288A1 (fr) Dispositifs microfluidiques
JP4800218B2 (ja) カリグラフィー用ペン形式の平面エレクトロスプレー・ソース及びその製造
US20050069949A1 (en) Microfabricated Fluidic Structures
US20050070010A1 (en) Dockable processing module
US20240230698A1 (en) Taylor cone emitter device automated handler, taylor cone emitter device automated handling system, and method for analyzing a sample

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20040720

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LI LU MC NL PT SE SI SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO

R17P Request for examination filed (corrected)

Effective date: 20040719

A4 Supplementary search report drawn up and despatched

Effective date: 20070802

17Q First examination report despatched

Effective date: 20100521

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20101002